Type 1 Diabetes TrialNet: Clinical Centers (U01)

描述(申请人提供)：1型糖尿病影响美国100多万人，其中大部分是儿童和年轻人，全世界还有更多的人。它发生在遗传易感的个体中，是免疫介导的胰岛分泌胰岛素的β细胞破坏的结果。目前对1型糖尿病的治疗，如果实施得当，可以延缓或预防糖尿病的长期并发症(即失明、肾功能衰竭和截肢)。然而，正确的糖尿病治疗是相当困难的，昂贵的，而且对糖尿病患者的生活方式非常有侵入性。糖尿病也是医疗费用的一个主要因素。是否有可能预防1型糖尿病或在糖尿病发展后保留胰岛素分泌？已经在遗传易感人群中尝试了几种免疫干预措施，但均未成功。其他试验也试图对1型糖尿病的病程进行早期干预，以保护β细胞功能。这些使用潜在毒性药物的免疫干预措施都失败了。因此，确定预防疾病或减缓疾病发展的药物将导致重大的医疗成本节约，并减少与糖尿病相关的并发症，此外，个人还可以节省大量的没有患病的费用。我们的长期目标是通过使用创新的基础疗法来预防1型糖尿病的发展，这些疗法旨在防止遗传易感个体的疾病发展。为了实现这一目标并响应RFA，这项申请的目标是完成TrialNet方案，并继续开发和测试创新的干预措施，以预防或减缓1型糖尿病的进展。其中一种延缓1型糖尿病进展的创新方法是我们建议的方案，“吡格列酮保护1型糖尿病患者的胰岛素分泌。”这项拟议的工作具有创新性，因为它利用了一种广泛使用的药物，这种药物毒性低，但具有免疫调节和消炎特性。我们还设计了一系列机制研究，以检查该药物的抗炎特性是否通过影响调节性T细胞发挥作用。 公共卫生相关性：这项研究的意义在于，预防1型糖尿病将节省数百万美元和巨大的人类痛苦。找出预防疾病或减缓疾病发展的药物，将大大节省医疗保健成本，并减少与糖尿病有关的并发症，此外，个人还可以节省大量不患糖尿病的费用。

DESCRIPTION (provided by applicant): Type 1 diabetes affects more than one million individuals, mostly children and young adults, in the United States and many more worldwide. It occurs in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin-secreting beta cells. The present treatment for Type 1 diabetes, when implemented properly, can delay or prevent the long-term complications of diabetes (i.e., blindness, renal failure, and amputation). However, proper diabetes treatment is quite difficult to do, expensive, and very invasive to the diabetic patient's lifestyle. Diabetes is also a major factor in health care costs. Is it possible to prevent Type 1 diabetes or to preserve insulin secretion once diabetes has develped? Several immune interventions have been tried in genetically susceptible individuals without success. Other trials have been attempted to intervene early in the course of Type 1 diabetes, in order to preserve beta cell function. These immune interventions using drugs with potential toxicity have failed. Thus, the identification of agents which either prevent the disease or slow its progression would result in major health care cost savings and reduce complications related to diabetes in addition to the huge individual savings in terms of not having the disease. Our long-term goal is to prevent the development of Type 1 diabetes through the use of innovative based therapies designed to prevent the development of the disease in genetically predisposed individuals. The objectives of this application, in pursuit of that goal and in response to the RFA, is completion of the TrialNet protocols and to continue to develop and test innovative interventions to prevent or slow the progression of Type 1 diabetes. One such innovative approach to slow the progression of Type 1 diabetes is our proposed protocol, "Pioglitazone Preserves Insulin Secretion in Type 1 Diabetes." The proposed work is innovative because it utilitizes a drug that is in wide spread use with low toxicity yet has immunomodulation and anti- inflamatory properties. We have also designed a series of mechanistic studies to examine whether the anti-inflammatory properties of the drug operate by influencing regulatory T-cells. PUBLIC HEALTH RELEVANCE: The significance of this research is that the prevention of type 1 diabetes will save millions of dollars and enormous human suffering. The identification of agents which either prevent the disease or slow its progression would result in major health care cost savings and reduce complications related to diabetes in addition to the huge individual savings in terms of not having the disease.